Prenatal aromatase inhibition alters postnatal immunity in domestic chickens (Gallus gallus).

In birds, exposure to exogenous testosterone during embryonic development can suppress measures of immune function; however, it is unclear whether these effects are due to direct or indirect action via aromatization. Estradiol (E2) is synthesized from testosterone by the enzyme aromatase, and this conversion is a necessary step in many signaling pathways that are ostensibly testosterone-dependent. Many lines of evidence in mammals indicate that E2 can affect immune function. We tested the hypothesis that some of the immunomodulatory effects observed in response to in ovo testosterone exposure in birds are mediated by conversion to E2 by aromatase, by using fadrozole to inhibit aromatization of endogenous testosterone during a crucial period of embryonic immune system development in domestic chickens (Gallus gallus). We then measured total IgY antibody count, response to PHA challenge, mass of thymus and bursa of Fabricius, and plasma testosterone post-hatch on days 3 and 18. Because testosterone has a reputation for immunosuppression, we predicted that if modulation of an immune measure by testosterone is dependent on aromatization, then inhibition of estrogen production by fadrozole treatment would lead to elevated measures of that parameter. Conversely, if testosterone inhibits an immune measure directly, then fadrozole treatment would likely not alter that parameter. Fadrozole treatment reduced circulating E2 in female embryos, but had no effect on males or on testosterone in either sex. Fadrozole-treated chicks had decreased day 3 plasma IgY antibody titers and a strong trend towards increased day 18 thymic mass. Furthermore, fadrozole treatment generated a positive relationship between testosterone and thymic mass in males, and tended to increase day 18 IgY levels for a given bursal mass in females. There was no effect on PHA response, bursal mass, or plasma testosterone at either age post-hatch. The alteration of several indicators of immune function in fadrozole-treated chicks implicates aromatization as a relevant pathway through which developmental exposure to testosterone can affect immunity in birds.

Screening for Zika virus in deceased organ donors in Florida.

Zika virus (ZIKV) cases have been detected across the United States (US) and locally acquired cases have been reported in Florida. Currently, there are no ZIKV screening guidelines and no data on the incidence among organ donors in the US. This retrospective study was conducted at Jackson Memorial-Miami Transplant Institute. Positive ZIKV tests in local deceased organ donors were investigated from 6/2016 to 1/2017. We evaluated demographics and risk factors for ZIKV infection among organ donors and transplant outcomes among recipients of donors with positive ZIKV testing. One hundred forty-two donors were analyzed. Ten percent had traveled to ZIKV-endemic countries and 19% had outdoor occupations. Only 3% had positive ZIKV IGG. None had a positive ZIKV IGM or PCR. ZIKV-positive donors were more likely to have traveled to ZIKV-endemic countries (50% vs. 9%, P = .05). The kidneys from a ZIKV-positive donor were transplanted in our hospital with no 6-month rejection, graft failure, or death in the recipients. Our study demonstrated a low prevalence of ZIKV among deceased donors in our community. Despite local ZIKV transmission, ZIKV was more common in donors who traveled to ZIKV-endemic countries. This cohort demonstrated excellent outcomes in recipients of ZIKV IGG-positive donors. However, larger studies are needed.

Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus-Infected Kidney Allograft Recipients.

In current practice, human immunodeficiency virus-infected (HIV(+) ) candidates with CD4 >200 cells/mm(3) are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm(3) among 38 anti-thymocyte globulin (ATG)-treated HIV-negative to HIV(+) kidney transplants performed at our center between 2006 and 2013. Median follow-up was 2.6 years. Rates of acute rejection and patient and graft survival were not different between groups. Occurrence of severe CD4 lymphopenia (<200 cells/mm(3) ), however, was more common among patients with a baseline CD4 count 200-349 cells/mm(3) compared with those transplanted at higher counts (75% vs. 30% at 4 weeks [p = 0.04] and 71% vs. 5% at 52 weeks [p = 0.001], respectively, after transplant). After adjusting for age, baseline CD4 count of 200-349 cells/mm(3) was an independent predictor of severe CD4 lymphopenia at 4 weeks (relative risk [RR] 2.6; 95% confidence interval [CI] 1.3-5.1) and 52 weeks (RR 14.3; 95% CI 2-100.4) after transplant. Patients with CD4 <200 cells/mm(3) at 4 weeks had higher probability of serious infections during first 6 months after transplant (19% vs. 50%; log-rank p = 0.05). These findings suggest that ATG must be used with caution in HIV(+) kidney allograft recipients with a pretransplant CD4 count <350 cells/mm(3) .

Demographics and prevalence of positive QuantiFERON-TB Gold In-Tube test in renal transplant candidates.

BACKGROUND: Latent tuberculosis infection (LTBI) screening prior to solid organ transplantation is standard of care. QuantiFERON-TB Gold In-Tube (QFT-GIT) test is the preferred diagnostic test for renal transplant candidates (RTC). QFT-GIT reversions and the potential delay of living-donor kidney transplantation (LDKT) because of QFT-GIT positivity have not been examined previously in RTC. METHODS: We evaluated the prevalence of positive QFT-GIT in RTC from January 1 through December 31, 2011. In addition, we examined the demographic and renal disease data differences between QFT-GIT-positive and -negative patients, changes in QFT-GIT results, and positive QFT-GIT results reverting to negative. Lastly, we evaluated if QFT-GIT-positive patients were less likely to undergo LDKT within 6 months of QFT-GIT testing. RESULTS: In total, 722 RTC were analyzed, 16% of whom had positive QFT-GIT. The QFT-GIT-positive patients were more likely to be older and foreign-born, P < 0.0001. Haitians had the highest prevalence. Of the 119 QFT-GIT-positive patients, 25% had low/intermediate-positive results and were more likely to revert to negative, compared with patients with high-positive QFT-GIT results (50% vs. 0%, P = 0.01). A trend was seen toward fewer QFT-GIT-positive patients undergoing LDKT, compared with QFT-GIT-negative patients (0% vs. 3%, P = 0.09). CONCLUSIONS: Our high prevalence was likely a result of the high number of foreign-born RTC. Half of our small subset of low/intermediate-positive QFT-GIT patients reverted to negative. QFT-GIT-positive patients were more likely to have their LDKT delayed.

Carbapenem-resistant Klebsiella pneumoniae infections in kidney transplant recipients: a case-control study.

INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections have emerged as a significant challenge in solid organ transplantation. CRKP infections in other patient populations have been associated with higher mortality, when compared to infections caused by carbapenem-sensitive K. pneumoniae (CSKP). AIMS: The aim of this study was to evaluate possible risk factors, clinical characteristics, and outcomes of CRKP infections compared with CSKP infections in kidney transplant recipients (KTR). METHODS: We retrospectively investigated 13 CRKP infections and 39 CSKP infections in KTR (2006-2010). RESULTS: CRKP was not significantly associated with age, gender, or comorbidities. CRKP infections were significantly associated with recent exposure to broad-spectrum antibiotics and were more likely to have been managed on an inpatient basis and to have required source control. CRKP was significantly associated with earlier mortality. Six of 13 (46%) patients with CRKP infection, and none of the patients with CSKP infection, died within 6.5 months of infection onset. Although cases and controls did not differ significantly with respect to diabetes, all patients (100%, n = 9) who died during the study had diabetes, while 58% of the 43 survivors had diabetes (P = 0.02). CONCLUSION: In conclusion, CRKP compared with CSKP is associated with greater risk of mortality. Investigations on ways to better prevent CRKP are urgently needed.

Left ventricular assist device exchange for persistent infection: a case series and review of the literature.

Left ventricular assist device (LVAD) exchange for control of infection may be an option for the treatment of persistent and severe infections of the LVAD. Data are limited regarding the indications for device exchange, methods for exchanging infected devices, post-exchange antimicrobial management, and outcomes of such patients. We report a series of cases in which an exchange was performed for persistent LVAD infection, review the literature on LVAD exchange and surgical techniques for these infectious complications, and suggest management strategies from a multidisciplinary perspective.

Favorable outcome in a renal transplant recipient with donor-derived infection due to multidrug-resistant Pseudomonas aeruginosa.

Most cases of donor-derived infection due to Pseudomonas aeruginosa reported in the literature are associated with vascular dehiscence, all of which resulted either in death or graft failure requiring graft removal. We report the successful treatment of donor-derived infection due to multidrug-resistant P. aeruginosa in a 64-year-old male who presented with bacteremia and peritransplant renal fluid collection after undergoing deceased-donor renal transplantation. As a result of the report of positive donor cultures by the host Organ Procurement Organization, the infection was promptly identified by blood cultures drawn before appearance of symptoms. Surveillance blood cultures in recipients are not usually recommended. However, they should be done if donor cultures turn positive. Therefore, it is crucial to perform cultures in donors and to closely follow them up for early identification and prompt treatment of donor-transmitted infections due to organisms like P. aeruginosa that can be graft and/or life threatening.

Does single dose salmeterol affect exercise capacity in asthmatic men?

The aim of this study was to investigate whether the long-acting beta-agonist salmeterol affects athletic performance in patients with asthma. The effect of 50 micrograms salmeterol on the cardiorespiratory responses to a progressive maximal cycle exercise test and on endurance capacity (defined as the exercise duration at 70% maximum oxygen uptake), was compared with 200 micrograms salbutamol and a matched placebo in eight asthmatic men. Both salmeterol and salbutamol improved pre- and postexercise forced expiratory volume in one second (FEV1) for maximal and endurance exercise. Following active treatment, patients exercised from a significantly high baseline FEV1, with both salmeterol (3.58(1.16)l) (mean (SD)) and salbutamol (3.55(1.24)l) compared with placebo (3.29(1.35)l). Similar improvements preceded endurance exercise. Cardiorespiratory, haemodynamic or subjective responses to the progressive maximum exercise tests were not different with salmeterol, salbutamol or placebo, nor did endurance capacity change with any treatment modality. Blood lactate levels, after 15 min exercise, were significantly higher with salbutamol (3.64 (1.83) mM), but not with salmeterol (3.03 (1.64) mM), compared with placebo (2.95 (1.69) mM). These results demonstrate the absence of significant cardiorespiratory or metabolic effects during exercise after a single dose of salmeterol, together with a lack-of ergogenic effect, as measured by maximal or endurance exercise performance, in patients with asthma.